The objective of this project is to study the biology of human pathogenic Leishmania in their phlebolomine sand fly vectors. The project involves the disciplines of parasitology, medical entomology, genetics, biochemistry and immunology. Laboratory-reared sand flies will be experimentally infected with a number of different Leishmania types and the following aspects of the parasites' biology in the insects will be studied: (1) the growth rate and development of the parasites within the sand fly gut, (2) the possibility of genetic exchange among Leishmania in the insect vector, (3) the mechanisms of sand fly susceptibility and resistance to leishmania infection, and (4) how the parasites attach and maintain themselves within the sand fly gut. Recently developed lines of the sand fly Phlebotomus papatasi, which are highly susceptible and refractory to L. major infection, will be utilized in this work. Collaborative research with scientists at Harvard University and the University of Alaska will be continued on other aspects of the biology of this vector-parasite interaction.